Scalable synthesis of bryostatin 1 and analogs, adjuvant leads against latent HIV.
basic_science · Level V
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- Record sourced from PubMed, PMID 29026042.
- Also identified by DOI 10.1126/science.aan7969 and PMC identifier 5714505.
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Abstract
Bryostatin 1 is an exceedingly scarce marine-derived natural product that is in clinical development directed at HIV/AIDS eradication, cancer immunotherapy, and the treatment of Alzheimer's disease. Despite this unique portfolio of indications, its availability has been limited and variable, thus impeding research and clinical studies. Here, we report a total synthesis of bryostatin 1 that proceeds in 29 total steps (19 in the longest linear sequence, >80% average yield per step), collectively produces grams of material, and can be scaled to meet clinical needs (~20 grams per year). This practical solution to the bryostatin supply problem also opens broad, facile, and efficient access to derivatives and potentially superior analogs.
Medical subject headings
- Adjuvants, Immunologic
- Anti-HIV Agents
- Bryostatins
- HIV Infections
- HIV-1
- Virus Latency